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PDIA3 protein disulfide isomerase family A member 3 [ Homo sapiens (human) ]

Gene ID: 2923, updated on 27-Nov-2024

Summary

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Official Symbol
PDIA3provided by HGNC
Official Full Name
protein disulfide isomerase family A member 3provided by HGNC
Primary source
HGNC:HGNC:4606
See related
Ensembl:ENSG00000167004 MIM:602046; AllianceGenome:HGNC:4606
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
P58; ER60; ERp57; ERp60; ERp61; GRP57; GRP58; PI-PLC; HsT17083; HEL-S-269; HEL-S-93n
Summary
This gene encodes a protein of the endoplasmic reticulum that interacts with lectin chaperones calreticulin and calnexin to modulate folding of newly synthesized glycoproteins. The protein was once thought to be a phospholipase; however, it has been demonstrated that the protein actually has protein disulfide isomerase activity. It is thought that complexes of lectins and this protein mediate protein folding by promoting formation of disulfide bonds in their glycoprotein substrates. This protein also functions as a molecular chaperone that prevents the formation of protein aggregates. [provided by RefSeq, Dec 2016]
Expression
Ubiquitous expression in thyroid (RPKM 333.0), prostate (RPKM 175.9) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See PDIA3 in Genome Data Viewer
Location:
15q15.3
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (43746438..43773278)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (41553795..41580638)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (44038636..44065476)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9318 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9319 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9320 Neighboring gene RNA, U6 small nuclear 354, pseudogene Neighboring gene CATSPER2 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6387 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9321 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9322 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44068605-44069133 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6388 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9324 Neighboring gene elongation factor for RNA polymerase II 3 Neighboring gene small EDRK-rich factor 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9325 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44081221-44081720 Neighboring gene SERF2-C15orf63 readthrough Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:44084013-44085212 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:44085666-44086519 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44087241-44087742 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44087743-44088242 Neighboring gene microRNA 1282 Neighboring gene serine incorporator 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:44091515-44092215 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:44092216-44092916

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Influence of the oxidoreductase ER57 on the folding of an antibody fab fragment. Mayer M, et al. J Mol Biol, 2004 Aug 20. PMID 15328618
  2. ER-60 (PDIA3) is highly expressed in a newly established serous ovarian cancer cell line, YDOV-139. Chay D, et al. Int J Oncol, 2010 Aug. PMID 20596667
  3. Disulfide isomerase ERp57 improves the stability and immunogenicity of H3N2 influenza virus hemagglutinin. Wu J, et al. Virol J, 2020 Apr 21. PMID 32316996, Free PMC Article
  4. Characterisation of a multimeric protein complex associated with ERp57 within the nucleus in paclitaxel-sensitive and -resistant epithelial ovarian cancer cells: the involvement of specific conformational states of beta-actin. Cicchillitti L, et al. Int J Oncol, 2010 Aug. PMID 20596672
  5. Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop. Liu Y, et al. J Exp Clin Cancer Res, 2019 Oct 30. PMID 31747963, Free PMC Article

See all (392) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PDIA3 driven STAT3/PD-1 signaling promotes M2 TAM polarization and aggravates colorectal cancer progression.
    Title: PDIA3 driven STAT3/PD-1 signaling promotes M2 TAM polarization and aggravates colorectal cancer progression.
  2. CircPDIA3/miR-449a/XBP1 feedback loop curbs pyroptosis by inhibiting palmitoylation of the GSDME-C domain to induce chemoresistance of colorectal cancer.
    Title: CircPDIA3/miR-449a/XBP1 feedback loop curbs pyroptosis by inhibiting palmitoylation of the GSDME-C domain to induce chemoresistance of colorectal cancer.
  3. Single-cell analysis identified PDIA3 as regulator of malignant characteristics and macrophage function in human cancers.
    Title: Single-cell analysis identified PDIA3 as regulator of malignant characteristics and macrophage function in human cancers.
  4. PDIA3 inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD.
    Title: PDIA3 inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD.
  5. Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation.
    Title: Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation.
  6. PDIA3 modulates genomic response to 1,25-dihydroxyvitamin D3 in squamous cell carcinoma of the skin.
    Title: PDIA3 modulates genomic response to 1,25-dihydroxyvitamin D(3) in squamous cell carcinoma of the skin.
  7. Interaction with ERp57 is required for progranulin protection against Type 2 Gaucher disease.
    Title: Interaction with ERp57 is required for progranulin protection against Type 2 Gaucher disease.
  8. PDIA3 Expression Is Altered in the Limbic Brain Regions of Triple-Transgenic Mouse Model of Alzheimer's Disease.
    Title: PDIA3 Expression Is Altered in the Limbic Brain Regions of Triple-Transgenic Mouse Model of Alzheimer's Disease.
  9. Protein disulfide isomerase A3 activity promotes extracellular accumulation of proteins relevant to basal breast cancer outcomes in human MDA-MB-A231 breast cancer cells.
    Title: Protein disulfide isomerase A3 activity promotes extracellular accumulation of proteins relevant to basal breast cancer outcomes in human MDA-MB-A231 breast cancer cells.
  10. Calreticulin and PDIA3, two markers of endoplasmic reticulum stress, are associated with metabolic alterations and insulin resistance in pediatric obesity: A pilot study.
    Title: Calreticulin and PDIA3, two markers of endoplasmic reticulum stress, are associated with metabolic alterations and insulin resistance in pediatric obesity: A pilot study.
Submit: New GeneRIF Correction See all GeneRIFs (140)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of protein disulfide isomerase family A, member 3 (PDIA3) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120/MBL complex co-localizes with the ER marker ERp57 and the Golgi marker p230 at subcellular perinuclear compartments in neuronal cells PubMed
env PDI is predominantly involved in HIV-1 entry and infection of the T cell line PM-1 and PHA-stimulated primary T lymphocytes, suggesting the preferential use of PDI relevant to the HIV-1 entry and establishment of virus reservoirs in resting CD4+ cells PubMed
env The disulfide cross-linking interaction between gp120 and PDI is enhanced by CD4 protein PubMed
env Protein-disulfide isomerase (PDI) cleaves disulfide bonds in recombinant HIV-1 envelope glycoprotein gp120, and gp120 bound to the surface receptor CD4 undergoes a disulfide reduction that is prevented by PDI inhibitors PubMed
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with PDIA3; predicted interaction to be within the endoplasmic reticulum and function as a thioredoxin reductase PubMed
env HIV-1 gp160 is identified to have a physical interaction with protein disulfide isomerase family A, member 3 (PDIA3) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
env Treatment of trimeric HIV-1 rgp140 with protein disulfide isomerase yields monomers by disruption of the intermolecular disulfide bonds PubMed
Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 is identified to have a physical interaction with protein disulfide isomerase family A, member 3 (PDIA3) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of protein disulfide isomerase A3 (PDIA3) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed
retropepsin gag-pol Positional proteomics analysis identifies the cleavage of human protein disulfide isomerase family A, member 3 (PDIA3) at amino acid residues 27-28 by the HIV-1 protease PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables cysteine-type endopeptidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables disulfide oxidoreductase activity TAS
Traceable Author Statement
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables phospholipase C activity TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein disulfide isomerase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein-disulfide reductase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in adaptive immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to interleukin-7 IEA
Inferred from Electronic Annotation
more info
  
involved_in extrinsic apoptotic signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in peptide antigen assembly with MHC class I protein complex IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in platelet aggregation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of extrinsic apoptotic signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in protein folding IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein folding in endoplasmic reticulum TAS
Traceable Author Statement
more info
 PubMed 
involved_in response to endoplasmic reticulum stress IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
part_of MHC class I peptide loading complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of Tapasin-ERp57 complex IPI
Inferred from Physical Interaction
more info
 PubMed 
is_active_in cell surface IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum TAS
Traceable Author Statement
more info
 PubMed 
located_in endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in focal adhesion HDA PubMed 
located_in melanosome IEA
Inferred from Electronic Annotation
more info
  
located_in nucleus HDA PubMed 
located_in phagocytic vesicle TAS
Traceable Author Statement
more info
  
located_in recycling endosome membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
protein disulfide-isomerase A3
Names
58 kDa glucose-regulated protein
58 kDa microsomal protein
ER protein 57
ER protein 60
disulfide isomerase ER-60
endoplasmic reticulum P58
endoplasmic reticulum resident protein 57
endoplasmic reticulum resident protein 60
epididymis secretory protein Li 269
epididymis secretory sperm binding protein Li 93n
glucose regulated protein, 58kDa
phospholipase C-alpha
protein disulfide isomerase-associated 3
NP_005304.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_005313.5 → NP_005304.3  protein disulfide-isomerase A3 precursor

    See identical proteins and their annotated locations for NP_005304.3

    Status: REVIEWED

    Source sequence(s)
    AC018512, AI769725, BC014433, BE644608, BG826781, BM854408
    Consensus CDS
    CCDS10101.1
    UniProtKB/Swiss-Prot
    P30101, Q13453, Q14255, Q8IYF8, Q9UMU7
    UniProtKB/TrEMBL
    A0A8I5KT88, V9HVY3
    Related
    ENSP00000300289.5, ENST00000300289.10
    Conserved Domains (1) summary
    cl27119
    Location:25 → 487
    YbbN; Negative regulator of GroEL, contains thioredoxin-like and TPR-like domains [Posttranslational modification, protein turnover, chaperones]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    43746438..43773278
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    41553795..41580638
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P30101.4 GenPept UniProtKB/Swiss-Prot:P30101

Gene LinkOut

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